Evidence map›Paper›PMID 22744337›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012

Protein kinase Cδ differentially regulates cAMP-dependent translocation of NTCP and MRP2 to the plasma membrane.

Se Won Park, Christopher M Schonhoff, Cynthia R L Webster, M Sawkat Anwer

Abstract read
In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. The Culprit Behind HBV-Infected Hepatocytes: NTCP.Drug design, development and therapy · 2024
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Nonalcoholic Steatohepatitis Modulates Membrane Protein Retrieval and Insertion Processes.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Article
  10. p38 MAPK α and β isoforms differentially regulate plasma membrane localization of MRP2.American journal of physiology. Gastrointestinal and liver physiology · 2016
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Organic anion uptake by hepatocytes.Comprehensive Physiology · 2014
    Review
  16. Review
  17. Effects of prostaglandin E2 on p53 mRNA transcription and p53 mutagenesis during T-cell-independent human B-cell clonal expansion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014
    Article
  18. Review
  19. Article
  20. INTRACELLULAR SIGNALING BY BILE ACIDS.Journal of bio-science · 2012
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Se Won ParkDepartment of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA.
Christopher M Schonhoff
Cynthia R L Webster
M Sawkat Anwer
Tufts University · US

Funding

MECHANISM OF CANALICULAR BILE FORMATION AND CHOLESTASISR01DK033436 · NIDDK · TUFTS UNIVERSITY BOSTON · PI ANWER, MOHAMMED SAWKAT · 1986 to 2010
$4.0M
Role of Protein Kinase C in Isoforms in Bile formation and CholestasisR01DK090010 · NIDDK · TUFTS UNIVERSITY BOSTON · PI ANWER, MOHAMMED SAWKAT · 2010 to 2014
$2.5M
cAMP modulation of bile induced hepatocyte apoptosisR01DK065975 · NIDDK · TUFTS UNIVERSITY BOSTON · PI LEVEILLE-WEBSTER, CYNTHIA R · 2005 to 2009
$1.1M
NIDDK NIH HHS DK33436NIDDK NIH HHS DK65975NIDDK NIH HHS DK90010NIDDK NIH HHS R01 DK065975NIDDK NIH HHS R01 DK090010
6 · The paper itself

Abstract

Cyclic AMP stimulates translocation of Na(+)/taurocholate cotransporting polypeptide (NTCP) from the cytosol to the sinusoidal membrane and multidrug resistance-associated protein 2 (MRP2) to the canalicular membrane. A recent study suggested that protein kinase Cδ (PKCδ) may mediate cAMP-induced translocation of Ntcp and Mrp2. In addition, cAMP has been shown to stimulate NTCP translocation in part via Rab4. The aim of this study was to determine whether cAMP-induced translocation of NTCP and MRP2 require kinase activity of PKCδ and to test the hypothesis that cAMP-induced activation of Rab4 is mediated via PKCδ. Studies were conducted in HuH-NTCP cells (HuH-7 cells stably transfected with NTCP). Transfection of cells with wild-type PKCδ increased plasma membrane PKCδ and NTCP and increased Rab4 activity. Paradoxically, overexpression of kinase-dead dominant-negative PKCδ also increased plasma membrane PKCδ and NTCP as well as Rab4 activity. Similar results were obtained in PKCδ knockdown experiments, despite a decrease in total PKCδ. These results raised the possibility that plasma membrane localization rather than kinase activity of PKCδ is necessary for NTCP translocation and Rab4 activity. This hypothesis was supported by results showing that rottlerin, which has previously been shown to inhibit cAMP-induced membrane translocation of PKCδ and NTCP, inhibited cAMP-induced Rab4 activity. In addition, LY294002 (a phosphoinositide-3-kinase inhibitor), which has been shown to inhibit cAMP-induced NTCP translocation, also inhibited cAMP-induced PKCδ translocation. In contrast to the results with NTCP, cAMP-induced MRP2 translocation was inhibited in cells transfected with DN-PKCδ and small interfering RNA PKCδ. Taken together, these results suggest that the plasma membrane localization rather than kinase activity of PKCδ plays an important role in cAMP-induced NTCP translocation and Rab4 activity, whereas the kinase activity of PKCδ is necessary for cAMP-induced MRP2 translocation.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsCell Culture TechniquesCell MembraneCyclic AMPGene Expression RegulationHumansMultidrug Resistance-Associated Protein 2Organic Anion Transporters, Sodium-DependentProtein Kinase C-deltaProtein Transportrab4 GTP-Binding ProteinsSymportersABCC2 protein, humanATP-Binding Cassette, Sub-Family C ProteinsCyclic AMPMultidrug Resistance-Associated Protein 2Organic Anion Transporters, Sodium-DependentProtein Kinase C-deltarab4 GTP-Binding Proteinssodium-bile acid cotransporterSymporters

Identifiers

PMID22744337
PMCPMC3468552
OpenAlexW2156770962

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.